Increased Arterial Carboxyhemoglobin Concentrations
in Chronic Obstructive Pulmonary Disease
Hiroyasu Yasuda, Mutsuo Yamaya, Katsutoshi Nakayama, Satoru Ebihara, Takahiko Sasaki, Shoji Okinaga,
Daisuke Inoue, Masanori Asada, Miyako Nemoto, and Hidetada Sasaki
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan
Rationale: Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory
pulmonary diseases. Objectives: To study whether arterial Hb-CO is
useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. Methods:
We measured arterial Hb-CO, arteriovenous Hb-CO differences, and
FEV1 in 58 patients with COPD and 61 ex-smoking control subjects.
Results: Arterial Hb-CO concentrations in patients at stable conditions were higher than those in control subjects (p ⬍ 0.0001).
Furthermore, the Hb-CO concentrations in patients at the exacerbations (p ⬍ 0.0001) were higher than those at the stable conditions.
Arterial Hb-CO concentrations in patients at stage III were higher
than those in patients at stage II, and the Hb-CO concentrations
in patients at stage IV were higher than those in patients at stage III
at the stable conditions and exacerbations. Arterial Hb-CO correlated
with exhaled CO in patients with COPD at stage II and stage III
at the exacerbations. Arterial Hb-CO inversely correlated with the
arterial blood partial oxygen pressure and FEV1. Arteriovenous
Hb-CO differences in patients at the exacerbations did not differ
from those in patients at stable conditions and from those in control
subjects. Moreover, arterial Hb-CO correlated with serum C-reactive
protein values and serum lipid peroxide concentrations. Conclusions:
These findings suggest that increased arterial Hb-CO may relate
to severity in patients with COPD because of lung and systemic
inflammation and production of reactive oxygen species.
Keywords: carbon monoxide; carboxyhemoglobin; chronic obstructive
pulmonary disease; heme oxygenase; systemic inflammation
Chronic obstructive pulmonary disease (COPD) is a major
global health problem that has an increasing disease burden and
effect on health care spending and is characterized by airflow
limitation that is not fully reversible (1). Various factors are
associated with the pathogenesis of COPD, including oxidative
stress (2), inflammatory cells (3, 4), such as activated neutrophils
and mononuclear leukocytes (5), and mediators, including tumor
necrosis factor ␣ (6, 7). Furthermore, these factors are associated
with the exacerbations of COPD (7–9) caused by airway infection
of viruses and bacteria (10, 11).
Many reports have suggested that airflow limitation presented
by FEV1 inversely correlates with several inflammatory indicators, such as nitric oxide (NO) levels in exhaled air (12, 13),
4-hydroxy-2-nonenal levels in the lung (14), and sputum
interleukin-8 levels and soluble tumor necrosis factor receptor
(4) in patients with COPD. NO, hydrogen peroxide, ethane, and
4-hydroxy-2-nonenal in exhaled air have been suggested to be
(Received in original form July 15, 2004; accepted in final form March 4, 2005)
Correspondence and requests for reprints should be addressed to Hiroyasu Yasuda,
M.D., Ph.D., Department of Geriatric and Respiratory Medicine, Tohoku University
School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. E-mail:
yasuda@geriat.med.tohoku.ac.jp
Am J Respir Crit Care Med Vol 171. pp 1246–1251, 2005
Originally Published in Press as DOI: 10.1164/rccm.200407-914OC on March 11, 2005
Internet address: www.atsjournals.org
noninvasive markers in monitoring the production of reactive
oxygen species in the lung, and inflammation in the airway and
lung in patients with COPD (12–17).
On the other hand, the inducible form of heme oxygenase
(HO), HO-1, is reported to be expressed in airway epithelial
cells (18), endothelial cells (19), and alveolar macrophages (20).
Carbon monoxide (CO) is produced endogenously by HO, and
is known to be present in measurable quantities in the exhaled
air of normal subjects (21, 22). Upregulation of HO-1 by oxidant
stress and proinflammatory cytokines (23) in airway and lung
inflammation is suggested to cause the increased levels of exhaled
CO in patients with inflammatory pulmonary diseases such as
bronchial asthma, acute pneumonia, silicosis, bronchiectasis, upper
respiratory tract infections (URTIs), and seasonal allergic rhinitis
(20, 22, 24–29). Arterial blood carboxyhemoglobin (Hb-CO)
concentrations correlate to exhaled CO concentrations (21), and
have also been suggested to be an inflammatory marker in inflammatory pulmonary disease, including bronchial asthma,
acute pneumonia, and silicosis (27–29). Blood gas analysis is
performed in patients with COPD not only at the first visit to
the hospital to estimate respiratory failure but also at visits to
the hospital because of exacerbations. The arterial Hb-CO concentrations can be measured at the measurement of blood gas.
However, Hb-CO concentrations at stable conditions and exacerbations have not been studied in patients with COPD.
In the present study, we studied the relationship between
Hb-CO concentrations and disease severity in patients with
COPD. We also measured the arteriovenous (a-v) Hb-CO concentration differences in patients with COPD to study the systemic and lung inflammation (28) in these patients (30, 31). Some
of the results of these studies have been previously reported in
the form of an abstract (32).
METHODS
Subjects
We studied 61 control subjects and 58 patients with COPD (Table 1).
Of patients with COPD, 28 were classified into stage II, 10 into stage III,
and 20 patients into stage IV according to the criteria by the Global
Initiative for Chronic Obstructive Lung Disease (33). To avoid the
influence of ambient CO on the Hb-CO, we enrolled subjects living
uptown in Sendai City in the Miyagi prefecture with the same environment as previously described (28). Furthermore, passive smokers in
patients with COPD and control subjects were excluded.
Exacerbations of COPD were defined with the criteria previously
described (11, 34). At the exacerbations, 18 of 58 patients had symptoms
of URTIs defined with the methods previously described (34). Type A
influenza virus was isolated from sputum from 7 of the 18 patients
with URTIs, and type B influenza was isolated from three patients. In
another 30 patients with COPD, 13 patients had acute bronchitis with
purulent sputum, and six patients had pneumonia. The patients with
exacerbated COPD had been receiving treatment as previously described (35).
None of the control subjects were receiving long-term medication.
All control subjects and all patients with COPD were ex-smokers. To
Yasuda, Yamaya, Nakayama, et al.: Carboxyhemoglobin in COPD
1247
TABLE 1. SUBJECT CHARACTERISTICS
Subject Category
Age (yr)
Male/female
(no.)
CRP (mg/dl)
FEV1
(%pred)
PaCO2 (mm Hg)
PaO2 (mm Hg)
Smoking History
(pack-yr)
Control (n ⫽ 61)
COPD (n ⫽ 58)
69.7 ⫾ 1.2
70.9 ⫾ 1.1
55/6
53/5
0.06 ⫾ 0.01
4.90 ⫾ 0.62*
95.5 ⫾ 0.8
48.9 ⫾ 2.2*
40.5 ⫾ 0.2
53.5 ⫾ 2.1*
90.2 ⫾ 0.8
64.4 ⫾ 1.7*
27 ⫾ 2
58 ⫾ 2*
Definition of abbreviations: COPD ⫽ chronic obstructive pulmonary disease; CRP ⫽ C-reactive protein.
Values are mean ⫾ SE.
* p ⬍ 0.0001.
exclude current smokers, we measured urinary cotinine concentrations
with high-performance liquid chromatography (36).
This study was approved by the Tohoku University Ethics Committee, and informed consent was obtained from each subject.
Measurement of Arterial and Venous Blood Hb-CO
and Exhaled CO
We took blood from the radial artery and the median cubital vein in
patients with COPD and in control subjects. We measured the Hb-CO
concentrations with a spectrophotometer (18, 27, 37), and calculated
the a-v Hb-CO concentration differences (28). We also measured exhaled CO concentrations in the control subjects and patients, as previously described (21, 22, 25, 26, 38). To avoid the influence of ambient
CO on Hb-CO, Hb-CO and exhaled CO levels were measured at least
3 hours after arrival in a room in the hospital with low ambient CO.
Measurement of Serum Lipid Peroxide
Concentrations of lipid peroxide (LPO) in arterial blood serum were
measured with methods as previously described (39, 40).
Study Protocol
We examined the relationships between arterial Hb-CO and either
exhaled CO, PaO2 and PaCO2, serum C-reactive protein (CRP), and LPO,
or FEV1.
Statistical Analysis
The age, sex, Hb-CO concentrations, a-v Hb-CO difference, exhaled
CO concentrations, arterial blood PaO2 and PaCO2 values, serum CRP
values, serum LPO concentrations, and FEV1 in each group are reported
as mean ⫾ SE. Statistical analysis of these values was performed by
one-way analysis of variance and followed by the Newman-Keuls test.
Linear regression analysis was performed using the method of least
squares, to compare the relationship between arterial blood Hb-CO
and either exhaled CO, PaCO2, PaO2, CRP value, LPO concentrations,
or FEV1 in patients with COPD at the exacerbations. Significance was
accepted at p ⬍ 0.05.
stable conditions. The Hb-CO concentrations were stable and reproducible between two measurements (0.81 ⫾ 0.02 vs. 0.82 ⫾
0.02%, n ⫽ 58, p ⬎ 0.50). Hb-CO concentrations in patients
with COPD at stable conditions (0.81 ⫾ 0.02%, n ⫽ 58) were
significantly higher than those in control subjects (0.55 ⫾ 0.02%,
n ⫽ 61, p ⬍ 0.0001; Figure 1). Among the patients with COPD
at stable conditions, Hb-CO increased in the severe stage of
COPD. Hb-CO concentrations in patients at stage III (0.83 ⫾
0.03%, n ⫽ 10, p ⬍ 0.05) were higher than those in patients at
stage II (0.70 ⫾ 0.03%, n ⫽ 24). Hb-CO concentrations in patients at stage IV (0.95 ⫾ 0.03, n ⫽ 20, p ⬍ 0.05) were also
higher than those in patients at stage III.
The arterial blood Hb-CO concentrations in all patients with
COPD at the exacerbations (1.09 ⫾ 0.04%, n ⫽ 58) were significantly higher than those at a stable condition before the exacerbations (0.81 ⫾ 0.02%, p ⬍ 0.0001; Figure 1). Furthermore,
among the patients at the exacerbations, Hb-CO increased in
the severe stage of COPD. At the exacerbations, Hb-CO concentrations in patients at stage III (1.12 ⫾ 0.05%, n ⫽ 10, p ⫽
0.0001) were higher than those in patients at stage II (0.85 ⫾
0.03%, n ⫽ 28). Hb-CO concentrations in patients at stage IV
(1.41 ⫾ 0.07%, n ⫽ 20, p ⫽ 0.01) were also higher than those
in patients at stage III. Furthermore, in patients at stage IV, the
Hb-CO changes between stable conditions and exacerbations
(0.47 ⫾ 0.05%) were higher than those in patients at stage III
(0.29 ⫾ 0.05%, p ⬍ 0.01), and the Hb-CO changes in patients at
stage III were higher than those in patients at stage II (0.14 ⫾
0.02%, p ⬍ 0.05).
RESULTS
Subject Characteristics
The subject characteristics of patients with COPD and control
subjects are shown in Table 1. There was no statistically significant difference in age and sex between normal control subjects
and patients. All control subjects and patients were ex-smokers.
Furthermore, urinary cotinine concentrations of all subjects were
less than 30 ng of the cotinine/mg creatinine ratio, showing that
all subjects in this study were not current smokers (22). The
patients were treated with sustained-release theophylline and
inhaled anticholinergic agents (oxitropium bromide). Furthermore, 10 of 58 patients were treated with inhaled corticosteroids
(beclometasone dipropionate or fluticasone propionate).
Arterial Blood Hb-CO Concentrations
To examine the reproducibility of the arterial blood Hb-CO
measurement in stable COPD, we measured the Hb-CO concentrations twice with a 4-week interval in patients with COPD at
Figure 1. Arterial blood carboxyhemoglobin (Hb-CO) concentration in
healthy ex-smoker control subjects (n ⫽ 61) and in patients with chronic
obstructive pulmonary disease (COPD; n ⫽ 58) at the exacerbations
and in patients with COPD at a stable condition before the exacerbations. The error bars indicate mean ⫾ SEM.
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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 171 2005
Hb-CO concentrations in patients with the symptoms of
URTIs (1.10 ⫾ 0.08%, n ⫽ 18) were higher than those in control
subjects (p ⬍ 0.0001) and those in patients at the stable conditions (0.82 ⫾ 0.04%, p ⬍ 0.0001), but did not differ from those
in patients without URTIs at the exacerbations (1.09 ⫾ 0.06%,
n ⫽ 40, p ⬎ 0.8).
Hb-CO concentrations in patients treated with inhaled corticosteroids did not differ from those in patients without inhaled
corticosteroids at the stable conditions (0.87 ⫾ 0.03 vs. 0.80 ⫾
0.03%, n ⫽ 10, p ⬎ 0.2) and at the exacerbations (1.24 ⫾ 0.08
vs. 1.06 ⫾ 0.05%, p ⬎ 0.1).
In the present study, the Hb-CO concentrations in ex-smoking
control subjects (n ⫽ 54) with a smoking history of more than
60 pack-years, which was the average smoking history of patients
in this study (Table 1), did not differ from the Hb-CO concentrations in the control subjects (n ⫽ 7) with a smoking history of
less than 60 pack-years (data not shown).
Venous Blood Hb-CO Concentrations
The venous blood Hb-CO concentrations were measured in 14
patients with COPD and 16 control subjects. The venous blood
Hb-CO concentrations in patients with COPD at a stable condition (0.71 ⫾ 0.04%, n ⫽ 14) were significantly higher than that in
control subjects (0.45 ⫾ 0.03%, n ⫽ 16, p ⬍ 0.0001). Furthermore,
among the patients at the stable condition, the venous blood
Hb-CO increased at the severe stage of COPD. The venous
blood Hb-CO concentrations in patients at stage IV (0.83 ⫾
0.05%, n ⫽ 6, p ⬍ 0.01) were higher than those in patients at
stage II (0.58 ⫾ 0.05%, n ⫽ 4). However, the venous blood
Hb-CO concentrations in patients at stage III (0.65 ⫾ 0.07%,
n ⫽ 4, p ⬎ 0.3) did not differ from those in patients at stage II.
Likewise, the venous blood Hb-CO concentrations in patients
at stage IV did not differ from those in patients at stage III
(p ⫽ 0.052).
The venous blood Hb-CO concentrations in all patients with
COPD at the exacerbations (1.02 ⫾ 0.09%, n ⫽ 14) were higher
than those at a stable condition (p ⬍ 0.0001). In contrast, among
the patients at the exacerbations, the venous blood Hb-CO did
not increase at the severe stage of COPD (data not shown).
A-v Blood Hb-CO Concentration Differences
To examine the site of endogenous production of CO, we measured the a-v blood Hb-CO concentration differences in patients
with COPD. In these patients, the a-v Hb-CO differences at a
stable condition (0.14 ⫾ 0.02%, n ⫽ 14) did not differ from those
in control subjects (0.13 ⫾ 0.03%, n ⫽ 16, p ⬎ 0.7). Furthermore,
among the patients at a stable condition, the a-v Hb-CO differences did not increase at the severe stage of COPD (data not
shown).
The a-v Hb-CO differences in all patients with COPD at the
exacerbations (0.16 ⫾ 0.03%, n ⫽ 14) did not differ from those
in control subjects (p ⬎ 0.5; Figure 2). Furthermore, among the
patients at the exacerbations, the a-v Hb-CO differences did not
increase with severity of COPD (data not shown).
The a-v Hb-CO differences in patients with COPD who had
URTIs also did not differ from those in patients without URTIs
at the exacerbations (data not shown).
Exhaled CO Concentrations
Exhaled CO concentrations in patients with COPD at the stable
conditions (3.5 ⫾ 0.1 ppm, n ⫽ 58) were significantly higher
than those in control subjects (1.8 ⫾ 0.1 ppm, n ⫽ 61, p ⬍
0.0001). In the patients at stage II and stage III, exhaled CO
concentrations (3.8 ⫾ 0.2 ppm, n ⫽ 38) at the exacerbations
were higher than those at the stable conditions (p ⬍ 0.001). In
Figure 2. Relationship between the arterial blood Hb-CO concentrations and FEV1 in patients with COPD (n ⫽ 54) at the exacerbations
(p ⬍ 0.0001, r ⫽ ⫺0.70).
contrast, in the patients at stage IV, exhaled CO concentrations
at the exacerbations did not differ from those at the stable
conditions (data not shown). Exhaled CO concentrations in patients with URTIs (4.0 ⫾ 0.2 ppm, n ⫽ 18) were also higher
than those in control subjects (p ⬍ 0.0001) and those in the patients at stable conditions (3.2 ⫾ 0.2 ppm, p ⬍ 0.05). Exhaled CO
correlated with the Hb-CO in patients at stage II and stage III
at the exacerbations (n ⫽ 38, r ⫽ 0.530, p ⬍ 0.001), but did not
correlate with the Hb-CO in patients at stage IV at the exacerbations (data not shown).
In patients with COPD at stage III, the exhaled CO concentrations in patients treated with inhaled corticosteroids (3.8 ⫾
0.5 ppm, n ⫽ 4) did not differ from those in patients without
inhalation of corticosteroids at the exacerbations (4.4 ⫾ 0.3 ppm,
n ⫽ 6, p ⬎ 0.3). Likewise, in patients at stage IV, the exhaled
CO concentrations in patients treated with inhaled corticosteroids (3.1 ⫾ 0.8 ppm, n ⫽ 5) did not differ from those in patients
without inhaled corticosteroids at the exacerbations (3.3 ⫾ 0.6 ppm,
n ⫽ 12, p ⬎ 0.8).
Factors Associated with Arterial Blood Hb-CO Concentrations
In patients with COPD at the exacerbations, arterial Hb-CO
concentrations inversely correlated with arterial blood PaO2 values (63.3 ⫾ 1.4 mm Hg, n ⫽ 58; r ⫽ ⫺0.70, p ⬍ 0.0001), and
correlated with arterial blood PaCO2 values (53.5 ⫾ 2.1 mm Hg,
n ⫽ 58; r ⫽ 0.52, p ⬍ 0.0001). Likewise, in the patients at the
exacerbations, arterial blood Hb-CO concentrations correlated
with serum CRP values (4.9 ⫾ 0.6 mg/dl, n ⫽ 58; r ⫽ 0.56,
p ⬍ 0.0001). Arterial Hb-CO concentrations also correlated with
serum LPO concentrations (5.63 ⫾ 0.39 nmol/ml, n ⫽ 58; r ⫽
0.56, p ⬍ 0.0001). Furthermore, in patients at the exacerbations,
the Hb-CO inversely correlated with FEV1 (n ⫽ 54, r ⫽ ⫺0.70,
p ⬍ 0.0001; Figure 2). On the other hand, in all four patients with
an Hb-CO of more than 1.4% at the exacerbations, FEV1 was
less than 40%, and in all eight patients with the Hb-CO of more
than 1.2% at the exacerbations, FEV1 was less than 50% (Figure 2).
DISCUSSION
The present study demonstrated that, at stable conditions, Hb-CO
concentrations in patients with COPD were higher than those
of control subjects. At stable conditions and exacerbations, the
Hb-CO concentrations in patients at stage III were higher than
those in patients at stage II, and the Hb-CO concentrations in
patients at stage IV were also higher than those in patients at
stage III. In patients at stage IV, the Hb-CO changes between
stable conditions and exacerbations were higher than those in patients at stage III, and the Hb-CO changes in patients at stage III
Yasuda, Yamaya, Nakayama, et al.: Carboxyhemoglobin in COPD
were higher than those in patients at stage II. In patients with
COPD at the exacerbations, Hb-CO concentrations also inversely correlated with FEV1 and arterial blood PaO2. At the
exacerbations, FEV1 was less than 40% in all four patients with
the Hb-CO concentrations of more than 1.4%, and FEV1 was
less than 50% in all eight patients with Hb-CO concentrations
of more than 1.2%. These findings suggest that measurement of
Hb-CO may be a useful marker of severity, especially to define
the severe exacerbations of COPD, although there is an overlap
of the Hb-CO concentrations between control subjects and patients with COPD and between patients with COPD at stable
conditions and exacerbations. The Hb-CO concentrations also
correlated with serum values of CRP and LPO, suggesting that
the Hb-CO concentrations might be also associated with the
lung and airway inflammation and production of reactive oxygen
species in the patients.
Smoking history in control subjects differed from that in
patients with COPD in the present study, although all control
subjects and all patients with COPD were ex-smokers. To avoid
the effects of ambient CO from smoking on Hb-CO and exhaled
CO levels, we excluded current smokers by measuring urinary
cotinine concentrations (41), and we confirmed that all subjects
had not smoked for at least 3 months before the samplings.
Furthermore, none of the control subjects and patients with
COPD was a passive smoker. On the other hand, the Hb-CO
concentrations in control subjects with a smoking history of more
than 60 pack-years, which was the average smoking history of
patients with COPD in this study, did not differ from the
Hb-CO concentrations in the control subjects with a smoking
history of less than 60 pack-years. These findings suggest that a
different smoking history did not influence the Hb-CO in the
control subjects.
Increased Hb-CO in patients with COPD in this study is
consistent with that observed in previous studies in patients with
bronchial asthma, pneumonia, and interstitial lung disease (27,
28), in which increased Hb-CO might relate to the inflammation
in airway and/or lung parenchyma. At stable conditions in this
study, airway inflammation (5) and production of reactive oxygen species (15) might be associated with increased Hb-CO (23)
in patients with COPD. Airway inflammation caused by infection
of bacteria and viruses (10, 11, 25) might further increase endogenous CO production in patients with COPD at exacerbations.
In patients with COPD at the exacerbations caused by bacterial and viral infections, PaO2 and FEV1 decrease and PaCO2 concentrations increase (10, 11). At the exacerbations in this study,
18 of 55 patients (31%) represented the symptoms of URTI, 13
patients (24%) had acute bronchitis with purulent sputum, and
six patients (11%) had pneumonia. The Hb-CO concentrations
might be increased through the production of proinflammatory
cytokines and NO (9, 23, 42–44) in airway virus infection, and
through reactive oxygen species (15, 23) from neutrophils (8) in
bacterial infection. These factors might also relate to the increased CRP and LPO levels (45, 46).
Systemic inflammation and production of reactive oxygen
species in the organs, including muscles, have been reported in
patients with COPD (30, 31). To examine the site of endogenous
production of CO, we measured the a-v Hb-CO difference, which
is a better way to define the site of inflammation, in the lung or
other organs, in patients with bronchial asthma and pneumonia
(28). In patients with COPD, the a-v Hb-CO differences at stable
conditions and exacerbations did not differ from those in control
subjects. Furthermore, among the patients with COPD at stable
conditions, the a-v Hb-CO differences in patients were not increased in the severe stage of COPD. The loss of a-v Hb-CO
differences in the patients in the present study suggests that CO
might be also produced in organs other than the lung, such as
1249
muscles (30). On the other hand, Hb-CO inversely correlated
with FEV1 in the patients at the exacerbations, suggesting that
lung and airway might be also the site of CO production.
The estimation of Hb-CO from exhaled CO measurements
is suggested to be inaccurate in patients with severe airflow
obstruction (47), and Hb-CO might be increased in patients with
severe airflow obstruction because of reabsorption of CO (47).
In fact, in patients with COPD at stage IV, exhaled CO concentrations at the exacerbations were lower than those at stable
conditions. Therefore, we performed direct measurement of
Hb-CO concentrations in the present study. Furthermore, increased exhaled CO concentrations were associated with increased Hb-CO concentrations in patients at the exacerbations
in patients at stage II and stage III. These findings suggest that
increased Hb-CO concentrations might represent the elevated
endogenous CO production, although the influence of reabsorption of CO on Hb-CO was not excluded.
We previously reported that arterial Hb-CO is correlated with
FEV1 in asthma exacerbations (28). This study also demonstrated
that the Hb-CO concentrations inversely correlated with FEV1
in patients with COPD. These findings suggest that airway narrowing might relate to the increased Hb-CO concentrations.
However, many mechanisms have been reported to be associated
with COPD exacerbations, including mucus hypersecretion, airway edema, and bronchoconstriction (48), all of which cause
airway narrowing. On the other hand, CRP values in patients
with COPD at exacerbations in this study were higher than those
in patients with bronchial asthma in the previous study (27).
The stronger inflammation in patients with COPD might be
associated with the greater Hb-CO concentrations in patients
with COPD compared with those in patients with bronchial
asthma (11). However, we could not estimate the effect of bronchoconstriction on Hb-CO in this study, because we did not
measure the changes in FEV1 after inhalation of anticholinergic
drugs or ␤-adrenergic stimulants.
In the present study, Hb-CO concentrations in patients with
COPD receiving inhaled corticosteroids did not differ from those
in patients with COPD without inhalation of corticosteroids.
Inhaled corticosteroids might fail to inhibit airway inflammation
in these patients with severe COPD with frequent exacerbations,
as demonstrated in patients with severe asthma (49).
Exhaled CO levels are reported to be low in patients deficient
in ␣1-antitrypsin (41). However, we did not examine the relationship between ␣1-antitrypsin levels and Hb-CO levels, because
␣1-antitrypsin deficiency in patients with COPD is very rare in
the Japanese population (50).
In summary, we have demonstrated that arterial Hb-CO concentrations increased in patients with COPD at a stable condition
compared with those in normal control subjects. The Hb-CO
concentrations at the exacerbations were significantly higher
than those at stable conditions. The patients needed to stop
breathing for 20 seconds to measure the exhaled CO concentrations. This procedure was difficult to repeat for the patients with
COPD with severe dyspnea. The Hb-CO concentrations can be
measured at the same time as the blood gas analysis, and should
be measured first at a medical examination. The measurement
of arterial Hb-CO concentration may be a simple and valuable
marker to monitor the severity of systemic and lung inflammation
and disease activities in patients with COPD.
Conflict of Interest Statement : H.Y. does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript; M.Y. does
not have a financial relationship with a commercial entity that has an interest in
the subject of this manuscript; K.N. does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript; S.E. does
not have a financial relationship with a commercial entity that has an interest in
the subject of this manuscript; T.S. does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript; S.O. does
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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 171 2005
not have a financial relationship with a commercial entity that has an interest in
the subject of this manuscript; D.I. does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript; M.A. does
not have a financial relationship with a commercial entity that has an interest in
the subject of this manuscript; M.N. does not have a financial relationship with
a commercial entity that has an interest in the subject of this manuscript; H.S.
does not have a financial relationship with a commercial entity that has an interest
in the subject of this manuscript.
Acknowledgment : The authors thank Grant Crittenden for the English correction.
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